http://repub.eur.nl/res/aut/7789/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/10480/ 2007-01-01T00:00:00Z Background: The effects of hemodialysis (HD) on left ventricular (LV) function have been studied by various echocardiographic techniques (M-mode, 2D echocardiography). These studies are hampered by a low accuracy of measurements because of geometric assumptions regarding LV shape. Three-dimensional echocardiography (3DE) overcomes this limitation. Methods: We tested the feasibility of 3DE assessment of LV function during HD. Conventional biplane Simpson rule (BSR) and single plane area length method (SPM) for LV function analysis were used as a reference. Results: 12 HD patients were studied and in 10 (83%) a total of 80 3D datasets were acquired. In 3 patients, one dataset (4%) was of insufficient quality and excluded from analysis. Correlation between SPM, BSR and 3DE for calculation of end-diastolic (EDV, r = 0.89 and r = 0.92, respectively), end-systolic volume (ESV, r = 0.92 and r = 0.93, respectively) and for ejection fraction (EF, r = 0.90 and r = 0.88, respectively) was moderate. Limits-of-agreement results for EDV and ESV were poor with confidence intervals larger than 30 ml. Both 2DE methods underestimated end-diastolic and end-systolic volume, while overestimating ejection fraction. Conclusion: 3DE is feasible for image acquisition during HD, which opens the possibility for accurate and reproducible measurement of LV function during HD. This may improve the assessment of the acute effect of HD on LV performance, and guide therapeutic strategies aimed at preventing intradialytic hypotension. http://repub.eur.nl/res/pub/6742/ 2005-03-30T00:00:00Z Chapter 1 is a brief introduction to several aspects of cardiovascular pressure-volume relations in dialysis patients. The aims of the thesis are presented. In Chapter 2, an overview is presented of circulatory physiology in hemodialysis (HD) patients. Volume withdrawal by ultrafiltration during HD may lead to intravascular hypovolemia and intradialytic hypotension. Hemodynamic defense mechanisms are discussed, focusing on left ventricular (LV) function. The concept of load, which reflects the interaction between the heart and the vascular system, is explained. Chronic pressure and volume overload account for a high prevalence of left ventricular hypertrophy (LVH) in dialysis patients. LVH may lead to LV dysfunction, which may eventually become manifest as heart failure. In dialysis patients, however, elevated cardiac filling pressures may reflect volume overload before HD rather than heart failure, and loading conditions are altered by volume witdrawal during HD. The cyclic changes in volume status hamper the assessment of LV function in HD patients. Current LV systolic and diastolic function measurements in clinical practice are reviewed. The load dependence of these measurements is discussed. Finally, future perspectives for load-independent assessment of LV function and measurement of pressure-volume relations in clinical dialysis practice are suggested. The cyclic changes in volume status and recurring cardiovascular strains of the HD procedure may lead to chronic myocardial damage, especially in patients with LVH or myocardial fibrosis. In these conditions, a decreased myocardial capillary density and reduction in myocardial flow reserve may lead to a reduced myocardial perfusion pressure during HD or volume overload before HD. In Chapter 3, we observed a high incidence of elevated cardiac troponin T (cTnT) measured in our entire dialysis population before a HD session. Although none of the patients had evidence of acute ischemic myocardial injury, baseline cTnT was elevated in 82%. The incidence of elevated cTnT was higher in patients with a history of cardiovascular disease. During a two-year follow-up period, patients with an elevated cTnT also had a higher mortality rate. In a subgroup, cTnT was measured during the HD procedure and no change in cTnT levels was found. We concluded that elevated cTnT levels in asymptomatic dialysis patients are of prognostic value. They are not caused by acute myocardial injury or by HD itself, but may be related to chronic myocardial damage or decreased clearance of cTnT degradation fragments. However, in dialysis patients who had an acute coronary syndrome during the follow-up period, cTnT increased above baseline, and tended to return to baseline after recovery. Therefore, a cTnT rise in dialysis patients above the individual baseline does appear to be diagnostic of acute myocardial injury. LV diastolic dysfunction is believed to be common in dialysis patients, especially in patients with LVH. However, as conventional echo Doppler parameters are load-dependent, predialysis hypervolemia may lead to pseudonormalization, and thereby mask diastolic dysfunction. In Chapter 4, we introduced new Doppler parameters of LV diastolic function. Mitral annulus velocity by Doppler tissue imaging (DTI) and LV inflow propagation velocity from color M-mode were measured before and after HD. Using these new echo Doppler techniques, which have been proposed as relatively preload-independent measurements of diastolic function, we demonstrated diastolic dysfunction in this study population. Unexpectedly, these techniques exhibited a pattern of load dependence similar to that displayed by the conventional Doppler measurements. So even when using the newer Doppler techniques, the degree of diastolic dysfunction was underestimated as a result of pseudonormalization due to volume overload. Therefore, the advantage of these techniques over conventional parameters for the assessment of LV diastolic function in dialysis patients is limited. Alternatively, DTI may reflect the actual diastolic function, which would imply that HD impaired cardiac relaxation and thereby worsened LV diastolic function. This could have been caused by the increase in serum ionized calcium concentration during HD. To further unravel the effects of changes in volume and in serum ionized calcium, we tested the effect of HD without ultrafiltration on these measurements, as was described in Chapter 5. Transmitral flow and mitral annulus velocities were measured before and after 1 hour of HD without ultrafiltration. The use of a standard 1.75 mmol/L dialysate Ca2+ concentration resulted in a significant increase in serum ionized calcium after one hour. Despite this increase, there was no change in transmitral flow and tissue Doppler velocities. This confirms the conclusion of the previous chapter, i.e. that the change in both transmitral Doppler and DTI results from changes in preload. Chronic pressure overload results from increased arterial stiffness, which becomes clinically manifest as systolic hypertension with an increased pulse pressure. A reduced aortic compliance signifies an increased cardiac pulsatile load, which promotes the development of LVH. In Chapter 6, a pulse pressure method is introduced, which is based on the Windkessel model, and can be used to estimate aortic compliance non-invasively. This technique, which combines carotid pulse contour analysis by applanation tonometry with aortic outflow volume measurements by Doppler echocardiography, has not been applied before in a dialysis population. We tested whether a reduction in volume overload by ultrafiltration during HD leads to an improvement of aortic compliance. After volume withdrawal, we observed a concomitant decrease in arterial pressure and a small improvement in aortic compliance. We concluded that the increase in aortic stiffness in dialysis patients is partly caused by a reversible reduction of aortic compliance due to volume expansion. Volume withdrawal by HD moves the arterial wall characteristics back to a more favorable position on the non-linear pressure-volume curve. LV systolic dysfunction is thought to contribute to an increased frequency of intradialytic hypotension. However, accurate measurement of LV function in dialysis patients is hampered by the load dependence of commonly used parameters, such as the LV ejection fraction (EF). The end-systolic pressure-volume relationship, or end-systolic elastance (Ees), represents the mechanical properties of a fully contracted ventricle. This inherent characteristic of a given LV is a parameter of LV systolic function which is almost insensitive to load. Ees was estimated non-invasively in hypotension-prone and hypotension-resistant dialysis patients from the acute LV response to preload reduction by nitroglycerine, as described in Chapter 7. EF, LV area and finger arterial pressure (Finapres) were recorded continuously before HD. Finapres and LV area data were combined to create pressure-area loops following intravenous nitroglycerine. Hypotension-prone and hypotension-resistant dialysis patients had similar Ees. Thus, it seems doubtful whether LV systolic function plays an important role in the genesis of intradialytic hypotension. Ees in both groups was low compared to Ees from pressure-area loops in non-uremic patients undergoing cardiac surgery. As EF before dialysis indicated normal systolic function, LV systolic dysfunction in dialysis patients is masked by the load dependence of conventional measurements. The measurement of LV pressure-volume relations yields valuable information on how the LV is coupled to the vascular system. This knowledge is essential in identifying dialysis patients with LV dysfunction. With this information, dialysis patients with heart failure can be distinguished from dialysis patients with excessive volume overload before HD, in whom lowering dry weight might suffice. Identification of dialysis patients with LV dysfunction at an earlier stage, i.e. before heart failure becomes clinically manifest, not only helps secondary prevention, but also provides a tool for measuring the results of treatment and intervention trials. Clinically applicable, load-independent measurement of LV function, therefore, could help improve the quality of life and management of our dialysis patients. http://repub.eur.nl/res/pub/10185/ 2003-01-01T00:00:00Z Left ventricular (LV) hypertrophy leads to diastolic dysfunction. Standard Doppler transmitral and pulmonary vein (PV) flow velocity measurements are preload dependent. New techniques such as mitral annulus velocity by Doppler tissue imaging (DTI) and LV inflow propagation velocity measured from color M-mode have been proposed as relatively preload-independent measurements of diastolic function. These parameters were studied before and after hemodialysis (HD) with ultrafiltration to test their potential advantage for LV diastolic function assessment in HD patients. Ten patients (seven with LV hypertrophy) underwent Doppler echocardiography 1 h before, 1 h after, and 1 d after HD. Early (E) and atrial (A) peak transmitral flow velocities, peak PV systolic (s) and diastolic (d) flow velocities, peak e and a mitral annulus velocities in DTI, and early diastolic LV flow propagation velocity (V(p)) were measured. In all patients, the E/A ratio after HD (0.54; 0.37 to 1.02) was lower (P < 0.01) than before HD (0.77; 0.60 to 1.34). E decreased (P < 0.01), whereas A did not. PV s/d after HD (2.15; 1.08 to 3.90) was higher (P < 0.01) than before HD (1.80; 1.25 to 2.68). Tissue e/a after HD (0.40; 0.26 to 0.96) was lower (P < 0.01) than before HD (0.56; 0.40 to 1.05). Tissue e decreased (P < 0.02), whereas a did not. V(p) after HD (30 cm/s; 16 to 47 cm/s) was lower (P < 0.01) than before HD (45 cm/s; 32 to 60 cm/s). Twenty-four hours after the initial measurements values for E/A (0.59; 0.37 to 1.23), PV s/d (1.85; 1.07 to 3.38), e/a (0.41; 0.27 to 1.06), and V(p) (28 cm/s; 23 to 33 cm/s) were similar as those taken 1 h after HD. It is concluded that, even when using the newer Doppler techniques DTI and color M-mode, pseudonormalization, which was due to volume overload before HD, resulted in underestimation of the degree of diastolic dysfunction. Therefore, the advantage of these techniques over conventional parameters for the assessment of LV diastolic function in HD patients is limited. Assessment of LV diastolic function should not be performed shortly before HD, and its time relation to HD is essential.